慢性心力衰竭患者應(yīng)用高強(qiáng)度間歇性有氧訓(xùn)練研究進(jìn)展

戴玫　付珞　胡建英　綜述　唐炯　審校

(1.成都市第三人民醫(yī)院心血管病研究所，四川 成都610031；2.成都市第三人民醫(yī)院康復(fù)醫(yī)學(xué)科，四川 成都610031)

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慢性心力衰竭患者應(yīng)用高強(qiáng)度間歇性有氧訓(xùn)練研究進(jìn)展

戴玫1付珞2胡建英1綜述唐炯1審校

(1.成都市第三人民醫(yī)院心血管病研究所，四川 成都610031；2.成都市第三人民醫(yī)院康復(fù)醫(yī)學(xué)科，四川 成都610031)

【摘要】高強(qiáng)度間隙性有氧訓(xùn)練能改善慢性心力衰竭患者的心肺儲(chǔ)備功能、提高運(yùn)動(dòng)耐力，改善內(nèi)皮功能、逆轉(zhuǎn)左室重構(gòu)，提高生活質(zhì)量，對(duì)左室射血分?jǐn)?shù)保留的心力衰竭、老年和女性患者同樣安全有效，但是目前均是樣本量較小的實(shí)驗(yàn)性研究，尚需多中心隨機(jī)研究以及長(zhǎng)期系統(tǒng)的回顧性和總結(jié)性研究成果來證實(shí)。

【關(guān)鍵詞】慢性心力衰竭；高強(qiáng)度間歇性有氧訓(xùn)練；預(yù)防；治療

據(jù)統(tǒng)計(jì)，全球慢性心力衰竭(chronic heart failure，CHF)患者達(dá)2 250萬，并且每年新增病例數(shù)200萬，中國(guó)心血管健康多中心合作研究抽樣調(diào)查 35～74歲城鄉(xiāng)居民15 518人，心力衰竭患病率為0.9%；隨著年齡增長(zhǎng)，心力衰竭的患病率顯著上升[1]。盡管如β受體阻滯劑、血管緊張素轉(zhuǎn)換酶抑制劑(angiotensin converting enzyme inhibitors，ACEI)、醛固酮受體拮抗劑等藥物的規(guī)范化使用和器械治療的進(jìn)展，心力衰竭仍是目前死亡的主要原因，CHF正在成為世界心血管領(lǐng)域的重要公共衛(wèi)生學(xué)問題。

許多臨床研究發(fā)現(xiàn)遵循個(gè)體化方案的體育鍛煉(physical activity) 和運(yùn)動(dòng)訓(xùn)練方案對(duì)CHF患者是安全有效的，能改善心力衰竭患者的臨床癥狀、運(yùn)動(dòng)耐量并延長(zhǎng)預(yù)期壽命[2-7]。其機(jī)制包括：控制心血管危險(xiǎn)因子，改善左心室收縮舒張功能、肺臟和骨骼肌功能、內(nèi)皮功能等[8]。因此，國(guó)內(nèi)外指南和共識(shí)均把規(guī)律性體育鍛煉和運(yùn)動(dòng)訓(xùn)練作為CHF規(guī)范化管理的一個(gè)重要部分?，F(xiàn)有數(shù)據(jù)顯示與中強(qiáng)度運(yùn)動(dòng)(moderate continuous training，MCT)比較，CHF患者更能適應(yīng)高強(qiáng)度間歇性有氧訓(xùn)練(high-intensity interval training，HIT)[9-10]。現(xiàn)就HIT在CHF患者中的應(yīng)用進(jìn)展進(jìn)行綜述。

1HIT

HIT是指多組高強(qiáng)度運(yùn)動(dòng)訓(xùn)練之間以低強(qiáng)度運(yùn)動(dòng)訓(xùn)練間歇進(jìn)行或以完全休息形成間歇期[11]。相對(duì)于心血管病患者而言，郭蘭等[12]定義HIT：進(jìn)行3～6組、每組2～5 min高強(qiáng)度運(yùn)動(dòng)訓(xùn)練，強(qiáng)度以75%～90%峰值攝氧量(peak oxygen uptake，VO2peak)為標(biāo)準(zhǔn)，在每?jī)山M高強(qiáng)度訓(xùn)練之間以較低強(qiáng)度的運(yùn)動(dòng)(50%～70% VO2peak)或完全休息形成間歇期。HIT的特點(diǎn)在于運(yùn)動(dòng)強(qiáng)度達(dá)到最大或接近最大的運(yùn)動(dòng)能力，但高強(qiáng)度運(yùn)動(dòng)時(shí)間相對(duì)較短，并可通過間歇期避免不適癥狀的出現(xiàn)，所以更容易被接受及完成。

Reindell和Roskamm提出“間歇訓(xùn)練” 的概念，并證實(shí)HIT能改善運(yùn)動(dòng)耐力、提高運(yùn)動(dòng)員成績(jī)[13]。學(xué)者們認(rèn)為，中央(心血管)和外周(骨骼肌)的良好適應(yīng)是有氧能力提高的原因[14-15]。出于安全性考慮，HIT多用于運(yùn)動(dòng)員，近年研究證實(shí)，CHF患者進(jìn)行HIT康復(fù)并無不良反應(yīng)。如在Koufaki等[16]的研究中，納入存在心力衰竭癥狀且射血分?jǐn)?shù)<45%的竇性心律患者，平均年齡59.1歲，隨機(jī)分為HIT組 (n= 8)和MCT組 (n= 9)訓(xùn)練6個(gè)月，結(jié)果發(fā)現(xiàn)相比MCT，CHF患者對(duì)HIT有良好的適應(yīng)性，在CHF患者中實(shí)施HIT是可行的。

2HIT對(duì)CHF患者的影響

2.1改善CHF患者心肺儲(chǔ)備功能

Wisl?ff等[17]進(jìn)行一項(xiàng)隨機(jī)研究，納入27例心肌梗死后穩(wěn)定心力衰竭患者[年齡(75.5±11.1)歲，射血分?jǐn)?shù)29%，VO2peak13 mL/(kg·min)]，規(guī)范化藥物治療基礎(chǔ)上隨機(jī)分入HIT組(每次訓(xùn)練4組，每組訓(xùn)練持續(xù)時(shí)間4 min高強(qiáng)度運(yùn)動(dòng)，達(dá)到90%～95%峰值心率，繼之3 min低強(qiáng)度運(yùn)動(dòng)恢復(fù)期，每次運(yùn)動(dòng)前后均有5～10 min熱身運(yùn)動(dòng)和整理運(yùn)動(dòng)，每周3次)和MCT組(運(yùn)動(dòng)強(qiáng)度達(dá)70%峰值心率)，共12～16周運(yùn)動(dòng)訓(xùn)練。結(jié)果顯示HIT組較MCT組VO2peak升高(46% vs 14%,P≤0.001)，提示運(yùn)動(dòng)耐力明顯改善。另兩項(xiàng)納入冠狀動(dòng)脈疾病患者的研究顯示，患者每周3～5次有氧間歇運(yùn)動(dòng)訓(xùn)練，訓(xùn)練強(qiáng)度為50%～95%VO2peak，12個(gè)月后VO2peak增加37%～42%[18-19]。但Pouleur等[20]的研究發(fā)現(xiàn)HIT組和MCT組VO2peak均較基線時(shí)增加，通氣閾增加，步行速度改善，兩組間無明顯差異，提示HIT比MCT在CHF并沒有更多獲益?，F(xiàn)有的臨床研究均是單中心、納入人數(shù)較少的研究，尚需更大規(guī)模、更高質(zhì)量的多中心研究證實(shí)。

2.2改善CHF患者心臟功能，逆轉(zhuǎn)左室重構(gòu)

心力衰竭大鼠模型顯示強(qiáng)度達(dá)到90%VO2peak有氧間歇訓(xùn)練能改善受損心肌細(xì)胞的收縮功能，減少心肌肥厚，降低血清心房腦鈉肽水平。Yu等[21]的研究顯示與心臟再同步化治療3個(gè)月后相似，HIT分別降低左室舒張末期容積18%和收縮末期容積25%。既往的研究證實(shí)ACEI能延緩心力衰竭進(jìn)程，CHF患者聯(lián)合ACEI和β受體阻滯劑治療能提高射血分?jǐn)?shù)12%[22]，CHF患者采用HIT訓(xùn)練得到相似的結(jié)論。研究顯示在藥物治療基礎(chǔ)上加用HIT可能會(huì)獲得更強(qiáng)的逆轉(zhuǎn)重構(gòu)的功效，而且射血分?jǐn)?shù)、每搏量、二尖瓣環(huán)運(yùn)動(dòng)、由組織多普勒成像測(cè)定的二尖瓣環(huán)收縮期速度等心肌收縮功能指標(biāo)得到明顯改善，HIT組左室舒張末期直徑和收縮末期直徑分別降低12%、15%，左室舒張末期容積和收縮末期容積分別降低18%、25%；評(píng)判心力衰竭預(yù)后和嚴(yán)重程度的指標(biāo)B型腦鈉肽前體降低40%[17]。這一結(jié)果與既往的研究結(jié)果血管緊張素Ⅱ受體拮抗劑氯沙坦改善心臟重構(gòu)和心肌功能相一致。因此，HIT可以作為心肌梗死后心力衰竭患者的有效康復(fù)訓(xùn)練方式。HIT對(duì)心力衰竭患者左室重構(gòu)的對(duì)照研究(Controlled study of myocardial recovery after interval training in heart failure The SMARTEX-HF)[23]是一項(xiàng)由歐洲7個(gè)中心共同參與的多中心研究，評(píng)估HIT、MCT及體育鍛煉3種不同的運(yùn)動(dòng)訓(xùn)練強(qiáng)度和模式對(duì)CHF患者左室重構(gòu)的影響，這是由歐洲心血管預(yù)防和康復(fù)委員會(huì)支持正在進(jìn)行的研究，期待這一大規(guī)模研究能成為心力衰竭患者運(yùn)動(dòng)訓(xùn)練領(lǐng)域的一個(gè)新突破。

2.3改善CHF患者內(nèi)皮功能、神經(jīng)內(nèi)分泌環(huán)境

內(nèi)皮功能不全會(huì)導(dǎo)致CHF患者運(yùn)動(dòng)耐受不良、心肌灌注受損、左室重構(gòu)，是心血管事件的獨(dú)立預(yù)測(cè)因子[24]。正如Linke等[25]研究顯示運(yùn)動(dòng)訓(xùn)練對(duì)CHF患者骨骼肌產(chǎn)生抗氧化效果。HIT較MCT增加抗氧化狀態(tài)15% (P=0.02)，改善內(nèi)皮功能介導(dǎo)的血管擴(kuò)張(R=0.67,P<0.01)，可能是因?yàn)镠IT增加一氧化氮的生物利用度，降低氧化應(yīng)激，提高抗氧化狀態(tài)。HIT比MCT更有效的原因尚不可知，但是推測(cè)可能與HIT患者具有更高對(duì)切應(yīng)力促發(fā)細(xì)胞水平甚或分子水平的機(jī)制有關(guān)。盡管研究顯示HIT改善一氧化氮介導(dǎo)的內(nèi)皮功能，但是運(yùn)動(dòng)訓(xùn)練組沒有發(fā)現(xiàn)內(nèi)皮素-1和胰島素樣生長(zhǎng)因子-1的改變，可能提示耐力訓(xùn)練通過其他途徑改善內(nèi)皮功能[17]。

2.4改善CHF患者生活質(zhì)量

Wisl?ff等[17，26]研究顯示HIT改善CHF患者生活質(zhì)量，其機(jī)制目前尚不清楚，可能與高強(qiáng)度運(yùn)動(dòng)增加患者的機(jī)體適應(yīng)性和運(yùn)動(dòng)能力有關(guān)。也有報(bào)道HIT改善CHF患者的焦慮抑郁狀態(tài)。

3HIT對(duì)特殊人群的影響

3.1HIT對(duì)左室射血分?jǐn)?shù)保留心力衰竭患者的影響

射血分?jǐn)?shù)保留的心力衰竭(heart failure with preserved ejection fraction，HF-PEF)患者可占到心力衰竭人群的50%[27]，HF-PEF首次發(fā)病后5年生存率為43%，總體病死率可能與射血分?jǐn)?shù)降低心力衰竭(heart failure with reduced ejection fraction，HF-REF)患者的病死率相當(dāng)[28]。HF-PEF的臨床研究(PEP-CHF、CHARM-Preserved、I-Preserve、J-DHF等)均未能證實(shí)對(duì)HF-REF有效的藥物如ACEI、血管緊張素Ⅱ受體拮抗劑、β受體阻滯劑等可改善HF-PEF患者的預(yù)后和降低病死率[29]?，F(xiàn)有小樣本臨床試驗(yàn)和數(shù)據(jù)報(bào)道[30-34]有氧耐力運(yùn)動(dòng)訓(xùn)練可以提高VO2peak，增加運(yùn)動(dòng)耐量，逆轉(zhuǎn)心房重構(gòu)，改善左心室舒張功能，改善生活質(zhì)量。但是仍需大規(guī)模隨機(jī)對(duì)照臨床研究結(jié)果評(píng)判HF-PEF患者最適合的運(yùn)動(dòng)訓(xùn)練模式。預(yù)防和治療舒張性心力衰竭患者的優(yōu)化運(yùn)動(dòng)訓(xùn)練模式研究(the optimising exercise training in prevention and treatment of diastolic heart failure study，OptimEx-CLIN)[35]是一項(xiàng)前瞻性隨機(jī)對(duì)照多中心研究，旨在研究HF-REF患者適合的運(yùn)動(dòng)訓(xùn)練劑量。擬納入180例穩(wěn)定HF-PEF患者，隨機(jī)(1∶1∶1)分為MCT、HIT和對(duì)照組，納入者最初3個(gè)月在嚴(yán)密的醫(yī)學(xué)監(jiān)控下進(jìn)行訓(xùn)練，繼之在遠(yuǎn)程醫(yī)療監(jiān)控下進(jìn)行9個(gè)月訓(xùn)練，研究要求觀察患者的運(yùn)動(dòng)能力改變情況，以及舒張功能、內(nèi)皮功能、生物學(xué)標(biāo)志物、生活治療的改變情況。這項(xiàng)研究于2014年7月開始納入病例，初步研究結(jié)果將于2017年發(fā)布。

3.2HIT對(duì)老年CHF患者的影響

老年患者心力衰竭患病率隨年齡增加而增加，有88%和49%的患者分別在65歲和80歲首次診斷心力衰竭[36]。老年CHF患者是否需要特殊的訓(xùn)練模式引起越來越多的爭(zhēng)論。但是，大量的臨床研究均未報(bào)道不同年齡患者采用功率車、跑臺(tái)或是阻力訓(xùn)練會(huì)引起嚴(yán)重的不良反應(yīng)[37-39]。Wisl?ff等[17]研究顯示HIT對(duì)老年CHF患者和心血管功能嚴(yán)重受損的患者是可行的。萊比錫老年心力衰竭患者運(yùn)動(dòng)訓(xùn)練干預(yù)研究(Leipzig Exercise Intervention in CHF and Aging Study，LEICA)[40]顯示55歲和65歲的老年CHF患者4周強(qiáng)化有氧耐力訓(xùn)練(每次訓(xùn)練4組，訓(xùn)練總時(shí)間20 min，每周5次)后VO2peak分別升高26%、27%。

3.3HIT對(duì)女性CHF患者的影響

臨床研究中，女性以運(yùn)動(dòng)為基礎(chǔ)的心臟康復(fù)參與率低于男性[41]。由于醫(yī)生和家庭支持有限，CHF患者合并癥多、骨骼肌系統(tǒng)疾病并存等因素是女性參與度低的主要原因[42-44]。但是女性在結(jié)構(gòu)化運(yùn)動(dòng)訓(xùn)練項(xiàng)目中的低參與率是一個(gè)嚴(yán)峻的現(xiàn)實(shí)，女性本就比男性基礎(chǔ)心功能差，因此有更高的殘疾風(fēng)險(xiǎn)。與男性相同程度的通氣功能和健康狀況比較，女性由于肌肉質(zhì)量偏低，VO2peak和6分鐘步行距離明顯低于男性。另一方面，參與運(yùn)動(dòng)訓(xùn)練的女性CHF患者可以得到與男性相當(dāng)程度的運(yùn)動(dòng)能力的提高，骨骼肌糖氧化分解酶活性的升高和生活質(zhì)量的改善[42]。所以強(qiáng)烈推薦女性CHF患者參加以結(jié)構(gòu)化運(yùn)動(dòng)訓(xùn)練為基礎(chǔ)的康復(fù)訓(xùn)練項(xiàng)目。

4小結(jié)

CHF是一組復(fù)雜的臨床綜合征，是各種心臟疾病的嚴(yán)重和終末階段。大量研究證實(shí)，對(duì)CHF患者進(jìn)行HIT是安全、有效的，HIT能改善其運(yùn)動(dòng)耐量和心功能和內(nèi)皮功能，提高生活質(zhì)量。因此，尚需進(jìn)一步探索和制定科學(xué)有效的運(yùn)動(dòng)訓(xùn)練強(qiáng)度和訓(xùn)練模式是心力衰竭治療領(lǐng)域未來的研究方向及新突破。

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基金項(xiàng)目：四川省衛(wèi)生廳科研課題 (100030)

作者簡(jiǎn)介：戴玫(1972—)，副主任醫(yī)師，碩士，主要從事心臟康復(fù)、心力衰竭研究。Email: daimei163126@126.com

【中圖分類號(hào)】R541.6

【文獻(xiàn)標(biāo)志碼】A【DOI】10.16806/j.cnki.issn.1004-3934.2016.03.014

收稿日期：2016-04-05修回日期：2016-04-13

Advances in Research on High-intensity Interval Training in Chronic Heart Failure

DAI Mei, FU Luo, HU Jianying, TANG Jiong

【Abstract】High-intensity interval training have positive effects on chronic heart failure with regard to reversal of cardiac remodeling, aerobic capacity, endothelial function, and quality of life , even in elderly and female patients with chronic heart failure , as well as on heart failure with preserved ejection fraction. Based on pilot studies, these results need to be verified by some randomized multi-center studies and systemic long-term retrospective cohort analysis.

【Key words】Chronic heart failure; High-intensity interval training; Prevention; Treatment